The present invention relates to the field of surgical pathology, in which a pathologist attempts to convey to a surgeon as rapidly as possible the presence and distribution of cancer in a resected surgical specimen. In particular, the present invention utilizes the biochemical specificity of injectable materials such as radiotracers with digital autoradiography techniques to image the specimen immediately after surgical resection.
Current surgical pathology practice consists of having a pathologist receive a surgical specimen immediately after resection. The pathologist marks the specimen with ink to show how the specimen was oriented in the body (i.e., the blue-inked side was facing forward in the body). The pathologist then slices the specimen into thin (i.e., 3 mm thick) slices, and visually inspects the slices. The pathologist then selects the areas that appear visually to have the greatest likelihood of containing cancer, and removes a small section from these pieces. The pathologist freezes these small pieces and shaves thin sections for rapid staining and inspection under a microscope (xe2x80x9cfrozen sectionxe2x80x9d) . The pathologist conveys his or her impression as to the frozen section results to the surgeon, so that the surgeon can decide whether the resection has been adequate. If the frozen section examination suggests that the cancer cells are very close to the margin of the surgical specimen, the surgeon is alerted that the xe2x80x9cmargins are not clearxe2x80x9d and that additional tissue needs to be removed to insure that the entire cancer is gone from the body. Theoretically, the surgeon could have the patient ready on the operating room table for additional removal of tissue pending the pathologists"" opinion as to whether this additional removal is needed. In practice, because frozen section examination is fairly inaccurate, most surgeons will not rely on the information from frozen section examination, and will simply complete their surgery and hope that when the final pathological report comes out (several days after surgery) the margins will have been shown to be clear of tumor. The risk of local recurrence of breast cancer is higher if the margins are not clear and if re-excision is not done. As a result, for breast cancer resections, in as many as 30% of cases, a re-excision is needed because the final pathology report comes back saying that the margins were not clear.
The present invention also pertains to the art of autoradiography. Autoradiography is a very old technique for using radiotracers in tissues to form images of radiotracer concentration in the tissues. Autoradiography is typically performed by injecting an animal with a radioactive tracer, sacrificing the animal, and then slicing the animal""s organs up and imaging the sliced organs with a detector that is sensitive to radiation emitted by the radioactive tracer. In nearly all cases, the autoradiography detector is sensitive to beta rays emitted by a radioactive tracer. The notable feature of autoradiography is that the specimen is placed in contact with the radiation detector, thereby improving spatial resolution.
The present invention also pertains to the art of radiotracer imaging of human cancers. Radiotracers consists of a chemical compound containing a component that is biologically specific (i.e., binds to a specific type of receptor, cell or organ), and a second component that emits radiation which can be detected by a device placed external to the body. For breast cancer imaging, the most widely used radiotracers are the positron-emitter 2-[F-18] fluorodeoxyglucose (also known as FDG) and the single-photon emitter Tc-99 m SestaMIBI (also known as MIBI). FDG can be detected with a positron emission tomography (also known as PET) scanner, or with a special device invented by the applying inventor known as a positron emission mammography scanner. MIBI can be detected with a gamma camera, or with a special device invented by the applying inventor known as a single photon emission mammography scanner. Several investigators have used hand-held gamma cameras or non-imaging gamma ray detectors in an operating room to examine the patient""s body prior to removal of a cancer, and after removal of a cancer. No investigators have imaged the radioactive cancer after removal from the patient""s body in order to assess whether the margins of resection were complete.
The present invention is novel in that it consists of the use of a radiation detector in conjunction with surgically-resected human tumors, in situations where the patient was injected with the cancer-seeking radiotracer prior to surgery. After the human tumor specimen is removed from the patient""s body, it is either imaged whole (i.e., without slicing) or is sliced and then the slices imaged with the radiation detector. The radioactive tracer can either be a gamma emitter like Tc-99 m labeled SestaMIBI, or it can be a beta emitter like 2-(F-18) Fluorodeoxyglucose.
The present invention is also novel in that it allows comparative imaging of the specimen by x-ray or other methods, and permits simultaneous display of the radiotracer and the x-ray images.
Nobody has imaged a human surgical specimen from a patient injected with radiotracers prior to surgery in order to describe the distribution of tumor in the specimen, and specifically to determine whether a tumor is wholly contained within the surgical specimen. Technically this approach is more easily accomplished than an intraoperative examination for several reasons: First, all the radiation is coming from the specimen when only the specimen is examined, whereas if we were to examine the tumor while it was in the patient we would have to remove the influence of radiation from parts of the body other than the surgical specimen. In the case of breast imaging, this xe2x80x9cscatterxe2x80x9d from parts of the body other than the breast is much greater than the radiation emitted by the breast, which can make it very challenging to see small tumors well.
The present invention provides surgeons with information as to the extent and location of cancers or other pathological processes immediately after removal of surgical specimens from the body. This information can help the surgeon decide whether the surgical procedure has been adequate for removal of the patient""s tumor, or whether additional tissues must be removed from the patient""s body. The current standard of medical care is to employ staining methods that provide such information several days after initial surgery, leading to the need for additional (i.e., re-excision) surgery and anesthesia, which inconveniences the patient and adds to health care costs. By providing early information about the distribution of cancer in the tissue specimen, the invention reassures the patient that initial surgery was most likely curative, and that no additional procedures are needed. Since the invention can rapidly assess whether cancer extends to the margins of the resected specimen, the surgeon can elect to keep the patient on the operating room table while the pathologist inspects the specimen with, the invention. If the invention demonstrates that cancer extends to the margins of the specimen, the surgeon can remove more tissue without subjecting the patient to the need for a separate surgical procedure (re-excision). The importance of the invention is illustrated by the fact that at centers of clinical excellence where surgeons perform lumpectomies for breast cancer, as many as a third of lumpectomies require re-excisions.
The present invention comprises an apparatus that is sensitive to a material which is administered to the patient prior to surgery, and which can be detected with the invention after removal of the surgical specimen. The material selectively accumulates in tumor cells, so that images of the surgical specimen with the invention provides information about the presence and distribution of tumor in the surgical specimen. The invention allows comparative anatomic images to be obtained of the surgical specimen so that the surgeon can measure the distance between tumor and the margin of the specimen. In this way the surgeon can assess the likelihood that the specimen margin will be free of tumor.
A primary objective of the present invention is to describe the distribution of cancer or precancerous conditions within a surgical specimen, for a patient who was injected with a substance prior to surgery, which substance concentrates selectively in cancer or precancerous cells (i.e., is tumor-seeking), said system preferably comprising:
a detector sensitive to the substance which is present in the surgical specimen and which selectively concentrates in the cancer or precancer; and
an apparatus capable of forming an image based on the information gathered by the detector, and which image describes the physical distribution of the substance in the surgical specimen rapidly so that a surgeon can be guided by the image provided by the apparatus; and
a holder capable of compressing the surgical specimen before and/or after slicing of the specimen against the detector so that the spatial resolution of the image is optimized.
A secondary objective of the invention is to compare the distribution of tumor-seeking substance with other descriptive maps, such as x-ray attenuation, said system preferably comprising:
a detector sensitive to the substance which is present in the surgical specimen and which selectively concentrates in the cancer or precancer; and
an apparatus capable of forming an image based on the information gathered by the detector, and which image describes the physical distribution of the substance in the surgical specimen rapidly so that a surgeon can be guided by the image provided by the apparatus; and
a holder capable of compressing the surgical specimen before and/or after slicing of the specimen against the detector so that the spatial resolution of the image is optimized; and
fiduciary markings upon the holder which are visible both on the image of the tumor-seeking agent, as well as on other methods of describing the distribution of tumor or anatomical information; and
a computer capable of using the fiduciary marker locations on each image set to register the tumor-seeking image with other image sets and to combine these image sets in order to derive useful information.
The present invention pertains to a system for describing to the physical distribution of an agent that accumulates selectively in tissue of a patient in an excised surgical specimen. The system comprises an agent which selectively concentrates in a cancer or precancer or focus of infection or other pathological condition. The system comprises a detector sensitive to the agent which is present in the surgical specimen. The system also comprises an apparatus capable of forming an image based on the information gathered by the detector, and which image describes the physical distribution of the agent in the surgical specimen so that a surgeon can be guided by the image provided by the apparatus, said apparatus connected to said detector.
The present invention pertains to a system for describing the physical distribution of an agent that accumulates selectively in tissue of a patient in an excised surgical specimen. The system comprises an agent which selectively concentrates in a cancer or precancer or focus of infection or other pathological condition. The system comprises a detector sensitive to the agent which is present in the surgical specimen. The system comprises an apparatus capable of forming an image based on the information gathered by the detector, and which image describes the physical distribution of the agent in the surgical specimen so that a surgeon can be guided by the image provided by the apparatus, said apparatus connected to said detector.